Brain imaging studies are starting to venture into the legal minefield of research into criminal psychopathy. Alison Abbott reports from one of the most controversial frontiers of neuroscience.

Cesare Lombroso, the nineteenth-century Italian criminologist, was the first to argue on scientific grounds that criminals are born, not made. Drawing on emerging theories of evolution and genetics, and the contemporary fad for phrenology, he concluded that those with a 'criminal mind' could be identified by deformations of their skulls. It all seemed reasonable at the time. But the facts did not fit the theory, and Lombroso's research was later discredited.

Today, many psychiatrists accept that some people who fall foul of the criminal justice system suffer from a condition — psychopathy — that is as much an illness as, for example, schizophrenia. Environmental factors may help to determine whether this 'illness' is expressed in the form of violent, criminal behaviour, but a growing number of experts argue that the underlying condition is biological. "More and more data are leading to the conclusion that psychopathy has a biological basis, and has many features of a disease," says Sabine Herpertz, a psychiatrist at the RWTH-Aachen University in Germany.

Several researchers are now using the latest brain imaging techniques in an attempt to find out what is different about the brains of psychopaths. They hope that these studies will lead to a fundamental biological understanding of psychopathy, and perhaps even to drug treatments for the condition.

Evaluation of Frontal Ventral Contribution to the Psychopathy Syndrome in a Cognitive Neuropsychological Context

Dominique Lapierre (Department of Psychology, UQAM)

Issues and Research Objectives

The purposel of this research is to establish the involvement of specific regions of the brain, the prefrontal ventral regions (orbital and median), in psychopathy.

The prefrontal regions of the brain include the frontal ventral regions and the frontal dorsolateral cortex. These two regions of the prefrontal lobe are closely linked to several other structures in the brain: they receive afferents from them and emit efferents to them. For each of the regions, the connections to other regions are different, implying specialization and different roles for each. Thus, the frontal ventral regions would then play a specific role in the processing of olfactory information. These regions would also handle integration of sensory information with that coming from the organism’s internal environment. The frontal ventral regions are also connected to the frontal dorsolateral cortex, a link that would be the basis of mediation of internal processes by external perceptions, according to the motivational significance accorded to these.

In addition to the analysis of the anatomical links between the various regions, the study of the effects of lesions also provides information on the functioning of the prefrontal regions. When lesioned, the functioning of these regions is disturbed and there appear deficits such as: lack of spontaneity, pathological inertia, impulsiveness, disinhibition and alteration of the consciousness of the self. The functions of the prefrontal regions include direction of attention, discrimination of the importance of stimuli, formation of intent, development of a plan of action, execution of the action and analysis of the results obtained. More specifically, the ventral regions are above all responsible for the social and emotional adjustment of the individual, whereas the dorsolateral regions are more centered on regulation and integration of the cognitive functions. When prefrontal lesions occur during childhood, the symptoms seem to demonstrate interference in the development of introspection, social judgment, empathy, abstract reasoning and planning.

Psychopaths have physical abnormalities in two key brain structures responsible for functions ranging from fear detection to information processing, a USC clinical neuroscientist has found in two studies that suggest a neuro-developmental basis to the disorder.

Adrian Raine, a professor of psychology and neuroscience in the USC College of Letters, Arts & Sciences, focused his research on two parts of the brain: the hippocampus, a portion of the temporal lobe that regulates aggression and transfers information into memory; and the corpus callosum, a bridge of nerve fibers that connects the cerebral hemispheres.

"Scientists have implicated different brain regions with respect to antisocial and aggressive behavior, and all are important and relevant," Raine said.

"But it goes beyond that to the wiring. Unless these parts of the brain are properly wired together, they'll never communicate effectively. They'll never result in appropriate behavior," he said.

Although the neurobiological roots of psychopathy are still being explored, the key behavioral features of a psychopath have been clearly defined

New research tools, from brain scans to psychological tests, are yielding more sophisticated insights into what makes psychopaths such cold-blooded predators, raising the prospect of improved tests to identify them and possibly even treatment.

''We can treat most other emotional disorders pretty successfully, and we will be able to treat this one soon,'' said Dr. James Blair, a researcher at the National Institute of Mental Health.

Psychologists estimate that one in every 100 people is unfeeling enough to qualify as a psychopath, with an especially heavy concentration among criminals. The ranks include serial killers such as Ted Bundy, who charmed and killed dozens of young women in the 1970s, and cannibal-murderer Jeffrey Dahmer, who fatally seduced 17 men and boys before he was caught in 1991, as well as a great many other people who never commit a crime punishable by law, but go through life heartlessly using and manipulating others without remorse.

Blair is an admitted optimist, but even skeptical scientists say that the last few years have brought progress, as researchers have largely reached agreement on how to define a psychopath and have begun pinpointing what happens in their brains.

Even the last few weeks have brought intriguing new findings. Among them: A psychological test designed to detect unconscious or frowned-upon attitudes picked up a decided tendency among psychopathic murderers to have abnormally positive attitudes toward violence, British researchers reported in the May 29 edition of the journal Nature.

No one has ever pinned down that attitude among psychopaths before, said Nicola Gray, coauthor of the Nature paper, because they relied on explicit questions, and psychopaths lie a lot.

Spinal taps on more than 50 imprisoned criminals in Sweden produced new evidence that psychopaths may have an imbalance of the brain chemicals serotonin and dopamine, according to a paper in last month's Journal of Neurology, Neurosurgery and Psychiatry.

Experiments using brain scanners while psychopaths perform various tasks also have been accumulating.

They suggest that ''the psychopath finds it difficult to process, handle, or use emotional material in the same way the rest of us do,'' said Robert D. Hare, professor emeritus of psychology at the University of British Columbia and widely considered the world's foremost authority on psychopaths.

Of course, that is the obvious problem, the very definition of a psychopath: They lack normal feelings, like empathy and remorse. And researchers have known for decades that psychopaths also tend to show some unusual physical responses: They sweat less and generally exhibit less distress when exposed to frightening or threatening stimuli, for example.

But research is now focusing on the brain abnormalities in psychopaths, said Dr. Bruce Price, chief of neurology at McLean Hospital in Belmont.

And, he said, ''the seismic shift is that, up until a decade or so ago, this was the realm of psychologists and sociologists. We now are at the point where biological science can try to make sense of this.''

That point has been reached partly thanks to new tools like brain scanners, researchers say, but also partly thanks to Hare's development of a broadly accepted clinical standard for who is a psychopath, a test called the PCL-R, or psychopathy checklist-revised

AbstractA prominent hypothesis of psychopathy posits it may result from abnormalities in orbital frontal cortex. However, damage to orbital frontal cortex does not lead to the full constellation of symptoms observed in psychopathy suggesting that other brain regions are implicated in the disorder. Here we report a study showing that incarcerated psychopaths’ brain potentials elicited by salient stimuli were characterized by abnormal late negativities that were more than twice the amplitude as those observed in incarcerated non psychopaths. The psychopath’s ERP abnormalities are similar to those observed in patients with temporal lobe damage. These data support the new hypothesis that psychopathy may best be conceptualized as a disorder of the paralimbic system – a system which embraces parts of the temporal lobe and frontal lobe, including orbital frontal cortex.

Psychopathy is a personality disorder defined by a cluster of interpersonal, affective and behavioral characteristics, including glibness, impulsivity, poor behavioral controls, and lack of empathy, guilt, and remorse

1,2. Psychopathic individuals are known to commit a disproportionately large amount of violent crime relative to non psychopathic individuals 3. Although there is agreement regarding the assessment and classification of psychopathy in forensic contexts, relatively little is known about the relevant brain disturbances. Historically, clinicians and researchers have made indirect inferences about the brain regions involved in psychopathy by examining changes in behavior following brain damage. For example, the case of Gage 4, which implicated the frontal lobes in psychopathic behavior 5,6. Subsequent studies of patients with frontal lobe damage suggest that orbital frontal cortex plays a pivotal role in mediating many behaviors related to psychopathy 7. Selective damage to the orbital frontal cortex leads to a condition termed ‘acquired sociopathic personality’ characterized by problems with motivation, empathy, planning and organization, impulsivity, irresponsibility, and insight. These data suggest that some aspects of psychopathy may map onto the (dys)function of orbital frontal cortex. However, the ‘acquired sociopathy’ model does not appear to fully account for the constellation of symptoms observed in psychopathy. For example, patients with orbital frontal damage rarely show instrumental or goal directed aggression – a cardinal feature of psychopathy 8. ‘Acquired sociopathic’ patients also do not exhibit the callousness commonly observed in psychopathic individuals. Similarly, patients with ‘acquired sociopathy’, unlike psychopathic individuals, are characterized by lack of insight and motivation, hoarding behavior, mood disturbances, and failure or inability to make long term plans. Psychopathic individuals, on the other hand, often enjoy making grandiose life plans – they just fail to follow through with them. Thus, while ‘acquired sociopathy’ appears to model some features of psychopathy, the two disorders differ in many respects. This raises the possibility that disturbances in brain regions other than orbital frontal cortex may contribute to psychopathy.

Studies employing event-related brain potentials (ERPs) in psychopathy have shown that during performance of a variety of cognitive and language paradigms psychopaths’ ERPs are characterized by late (500 ms post-stimulus on average) negativities 9-13. The psychopaths’ late ERP negativities are often two to three times the size as those observed in control participants. One common denominator of the studies which have observed late ERP negativities in psychopaths is that the eliciting stimuli were task relevant or salient. That is, the experimental context was manipulated in such a way as to require the participants to immediately process the stimuli. However, the interpretation that the primary processing deficit in psychopaths is related to the salience of the stimuli is hampered by the fact that the tasks shown to elicit the late ERP abnormalities in psychopaths often included relatively complex stimuli and decision making tasks. Thus, it has been difficult to isolate the neurocognitive processes underlying the late ERP negativities observed in psychopaths. Here we use an auditory ‘oddball’ task to selectively manipulate the salience of the stimuli. In oddball tasks, participants are instructed to respond (or count) low probability stimuli (i.e., salient stimuli) and to discriminate them from frequently occurring standard stimuli. The oddball task has been extensively studied and the elicited ERPs are abnormal in a variety of disorders, such as schizophrenia, depression and alcoholism. The neural systems engaged in oddball target detection are well understood and include structures in the inferior lateral frontal cortex and medial and anterior lateral temporal lobes 14-20. Our primary prediction was that during processing the salient stimuli psychopaths’ ERPs would be characterized by late ERP negativities. ERPs were recorded from 80 incarcerated participants, classified into psychopathic and nonpsychopathic groups according to scores on the Hare Psychopathy Checklist-Revised (PCL-R) 1, while they performed an auditory ‘oddball’ target detection task. Consistent with our hypothesis, analyses of the electrophysiological data revealed that psychopathic inmates, relative to demographically matched nonpsychopathic inmates, showed an aberrant large late ERP negativity during target detection (N550; see Figures 1-4). Psychopaths also had an enlarged N2b and a slightly reduced fronto-central P3 during target detection. The N550 ERP negativity was nearly twice the amplitude in psychopaths as in nonpsychopaths (see Figures 1 and 4). These data demonstrate that a simple salient stimulus discrimination between two tone types is sufficient to elicit the late ERP negativities in psychopaths. Thus, the late ERP negativities do not appear to be necessarily related to language stimuli or other complex task demands. However, the functional significance of these late ERP negativities in psychopaths still remains unclear. The auditory oddball task has been well studied in psychiatric patient populations and in patients with neurological conditions. Examination of this literature reveals that ERP studies of auditory oddball target detection in patients with selective damage to medial and anterior lateral temporal lobe indicate that abnormalities in the scalp recorded waveforms include a large early negativity (N2b), mildly reduced fronto-central positivity (P3), and an enlarged late negativity (N550) 21-23. This sequence of electrophysiological abnormalities appears to be exclusive to patients with medial and anterior lateral temporal lobe lesions or damage (see Figure 4). That is, these abnormalities have not been observed in patients with frontal lobe or parietal lobe damage during similar tasks 21,24. A comparison of the ERPs elicited by salient target stimuli for the psychopaths and the patient studies are shown in Figure 4. The similarities exist at the multiple ERP components with the enhancement of the N2b, mild reduction of the P3, and enlarged late ERP negativity. Additional support for the view that psychopathy is associated with medial and anterior lateral temporal lobe function comes from hemodynamic imaging studies of psychopathy 25-27. These studies suggest that during processing of certain types of linguistic and emotional stimuli the anterior superior temporal gyrus 25, amygdala 26,27, and hippocampus 28appear to be dysfunctional in psychopaths relative to controls. Further support for the hypothesis of abnormal medial and anterior lateral temporal lobe function in psychopathy comes from behavioral studies in patients with temporal lobe epilepsy. There is some evidence that suggests patients with temporal lobe epilepsy have a high incidence of psychopathic-like behavior 29.

Page 6 Removal of the dysfunctional anterior temporal lobe in these epilepsy patients appears to reduced hostility, increase warmth and empathy in social relationships and decrease inappropriate sexual behavior 29. Overall, these converging results are consistent with the hypothesis that medial and anterior lateral temporal lobe structures play a prominent role in psychopathy. It is relevant to note the medial and anterior lateral aspects of the temporal lobe may be conceptualized as part of the larger paralimbic system. The paralimbic system, defined by similarities in the structure of neurons and number of layers of cortex, was described by Brodmann (1909). The paralimbic system embraces classic limbic structures such as the amygdala and hippocampus and also includes anterior superior temporal gyrus, cingulate cortex and, interestingly, the orbital frontal cortex. Abnormalities in several functions of this circuitry, including error monitoring, response inhibition, and affective processing, have been observed in psychopathy. For example, regional abnormalitiesduring affective processing have recently been observed in the anterior and posterior cingulate in psychopathy 26. Additionally, brain imaging studies 30and behavioral studies of patients with brain damage to the anterior cingulate 31suggest this structure also plays a prominent role in response inhibition, a process consistently found to be dysfunctional in psychopathy 10,32. It is probable that the orbital frontal cortex plays a crucial role in the neuronal circuitry involved in psychopathy. However, dysfunction of the orbital frontal cortex does not fully account for the constellation of symptoms that comprise psychopathy. A broader view, including medial and anterior lateral temporal lobe structures and perhaps other regions of the paralimbic system, appears to account more fully for the diverse symptoms observed in psychopathy. In summary, the data from the present study suggest that psychopathy is associated with functional abnormalities in the medial and anterior lateral aspects of the temporal lobe. The medial and anterior lateral aspects of the temporal lobe are part of a larger paralimbic system which includes the anterior and posterior cingulate and orbital frontal cortex. These results, in conjunction with converging evidence from Page 7 electrophysiological and hemodynamic studies in psychopathy and with studies of lesion patients, suggest that psychopathy may best be conceptualized as a disorder of the paralimbic system rather than a disorder of a single brain region (i.e., orbital frontal cortex).

Page 8 Methods Participants. A total of 80 male inmates (ages 18-55) from a maximum-security prison near Vancouver, British Columbia volunteered for the study. Participants were free from any reported serious head injury or neurological impairment and had no DSM-IV Axis I diagnosis. IQs were normal to above normal and the mean years of formal education were greater than 10 years. The Hare Psychopathy Checklist-Revised was used to assess psychopathy 1. Inmates with a PCL-R score of 30 or above were defined as Psychopaths (n=41; mean PCL-R score 33.1 (SD 2.04)) and those with a PCL-R score below 30 were defined as Nonpsychopaths (n=39; 20.61 (SD 6.17)). Inter-rater reliability for two raters for a subset of the inmates (n=30) was .83. The mean age and years of formal education were 32.3 and 33.8, and 10.7 and 11.3 years for Psychopaths and Non Psychopaths, respectively. The National Adult Reading Test (NART) and Quick tests were used to assess IQ. NART and Quick scores for Psychopaths were 110.4 (SD 8.6) and 104.2 (SD 11.4) and for Nonpsychopaths they were 109.1 (SD 9.9) and 104.6 (SD 8.8), respectively. There were no group differences in age, years of formal education, NART or Quick scores (all Psychopath’s > .50). Each inmate was paid $5.00 for the PCL-R interview and $10.00 for the experiment. The total of $15.00 was equivalent to 2 days prison wage. The study was approved by Institutional and University ethical review boards, and participants gave written informed consent. Stimuli. The target (1500 hz tones), novel (e.g., random sounds) and standard (1000 hz tones) stimuli were presented with a probability of .10, .10 and .80, respectively (200 ms duration; 1000-1500 ms random inter-stimulus interval). Participants were instructed to respond as quickly and accurately as possible (hand counterbalanced across participants) to the target stimuli and to ignore the standard and novel stimuli.

10P3 peak amplitude analyses. There were no significant group differences at midline sites in the amplitude of the P3 for any stimuli. However, there was a significant correlation between the amplitude of the P3 and psychopathy scores at frontal (r= -. 23, Psychopath < .05 at scalp site F8) and central sites (r= -.19, Psychopath < .05 at scalp site C4). N550 peak amplitude analyses. The N550 elicited by target stimuli was significantly larger for Psychopaths than for Nonpsychopaths at frontal and central sites (Group x Condition x Site interaction: F (10, 740) = 2.84, Psychopath < .024 – Greenhouse-Geisser).

Acknowledgements: This research was supported in part by grants from the Medical Research Council (MRC) of Canada, the British Columbia Health Services, the British Columbia Medical Services Foundation and funds from the Schizophrenia Division, Department of Psychiatry, University of British Columbia. The first author was supported by the Michael Smith Graduate Scholarship, Medical Research Council of Canada. The second author was supported by a Natural Sciences and Engineering Research Council of Canada Fellowship. These data were collected while the authors were at the University of British Columbia. We would like to thank the staff and inmates at the Regional Health Center, Abbotsford, B.C., Canada for their support and cooperation.

The next time you find yourself wondering, “Teenagers! Why do they do that?”, look to their adolescent brains. New research suggests that the risk-taking behaviors seen in adolescents may be attributed to their still developing brains. Another study explores the brain basis for the risk-taking behaviors of psychopaths.

New research—in both humans and animals—shows differences in the structure and functioning of adolescent brains compared with preadolescents or adults that correspond to such teenage behaviors as immature decision making, increased risk taking, and impulsive behaviors. As a result of this research, scientists now urge that puberty be studied as a separate stage of development—one distinctly different from the life stages of children or adults.

“Adolescents' brains seem to bias their decision-making capabilities in the direction of favoring short-term benefits, even when these benefits are weighed against potential long-term detriments,” says Jonathan Cohen, MD, PhD, of the department of psychology at Princeton University.

In one study, Gregory Berns, MD, PhD, and his colleagues at Emory University School of Medicine found that hyperactivity in the reward circuits of adolescent brains compared with adult brains may underlie adolescents' immature decision making.

Weaker brain links found in psychopathsDecreased communication between emotional and executive centers may contribute

By Laura Sanders 11/30/11

Brain differences might help explain psychopaths’ cold, calculated and often antisocial behavior, and perhaps even point out better ways to treat or prevent the disorder, a study of Wisconsin prison inmates suggests.

Compared with a group of 13 non-psychopathic criminals, a group of 14 psychopaths had weaker connections between an area near the front of the brain called the ventromedial prefrontal cortex, or vmPFC, and the amygdala, a pair of almond-shaped structures deep in the brain. Earlier studies have hinted that this particular link is important for emotional regulation and aggression.

Neuroscientist Michael Koenigs of the University of Wisconsin–Madison and colleagues discovered the weaker connection by taking a mobile brain scanner to a medium-security prison. Psychopaths are overrepresented in prison populations thanks to their lack of empathy and tendency toward antisocial behavior.

After interviewing inmates and scrutinizing their disciplinary records to determine whether they were psychopaths, the scientists conducted two kinds of brain scans. The first measured the strength of brain connections called white matter tracts, which are bundles of nerves that serve as information superhighways that shuttle information between different brain regions. It was those scans that revealed the weaker link between the vmPFC and the amygdala in psychopaths, the team reports November 30 in the Journal of Neuroscience.

In the second kind of brain scan, the team assessed which brain regions were coordinating their activity while the prisoners were daydreaming. Normally, the vmPFC and right amygdala work in tandem. But in psychopaths this coordination is lower, the team found.

Finding a breakdown in vmPFC connections was particularly intriguing to Koenigs. Neurologists have long observed that after damage to this area, people can take on personality traits that are reminiscent of psychopathy, including diminished empathy and irresponsible behavior. The results offer direct evidence that the link between the vmPFC and the amygdala is compromised in psychopaths.

“This article does a marvelous job of integrating what we know about brain function,” says experimental psychologist Robert Hare of the University of British Columbia in Vancouver, who was not involved in the study. “What’s striking is that it’s confirming what clinicians have suspected and discussed and talked about. Now we’re getting down to the real nitty-gritty here.”

Hare cautions that identifying what’s different in the brains of psychopaths isn’t the same thing as figuring out the cause of psychopathy. The weakened connections seen in the Wisconsin study could be a by-product of some other environmental or genetic factor commonly found among psychopaths.

“We have a chicken and an egg, in a sense,” he says. “There’s a tendency, certainly among people in the criminal justice system, to take any of these deficits and say, ‘Wow, we have a psychopath who has all these behavioral problems, and now we have this brain anomaly or dysfunction that seems to match, therefore one caused the other.’”